High-Density Lipoprotein Metabolism in Human Apolipoprotein B\u3csub\u3e100\u3c/sub\u3e Transgenic/Brown Adipose Tissue Deficient Mice: A Model of Obesity-Induced Hyperinsulinemia

Obese and diabetic humans display decreased plasma high-density lipoprotein cholesterol (HDL-C) concentrations and an increased risk for coronary heart disease. However, investigation on HDL metabolism in obesity with a particular emphasis on hepatic ATP-binding cassette transporter A1 (ABCA1), the primary factor for HDL formation, has not been well studied. Human apolipoprotein B100 transgenic (hApoBtg) and brown adipose tissue deficient (BATless) mice were crossed to generate hApoBtg/BATless mice. Male and female hApoBtg and hApoBtg/BATless mice were maintained on either a regular rodent chow diet or a diet high in fat and cholesterol until 24 weeks of age. The hApoBtg/BATless mice that were fed a HF/HC diet became obese, developed hepatic steatosis, and had significantly elevated plasma insulin levels compared with their hApoBtg counterparts, but plasma concentrations of total cholesterol, HDL-C, triglycerides, and free fatty acids and lipoprotein distribution between genotypes were not significantly different. Hepatic expression of genes encoding HDL-modifying factors (e.g., scavenger receptor, class B, type I, hepatic lipase, lecithin:cholesterol acyltransferase, and phospholipid transfer protein) was either altered significantly or showed a trend of difference between 2 genotypes of mice. Importantly, hepatic protein levels of ABCA1 were significantly lowered by ∼35% in male obese hApoBtg/BATless mice with no difference in mRNA levels compared with hApoBtg counterparts. Despite reduced hepatic ABCA1 protein levels, plasma HDL-C concentrations were not altered in male obese hApoBtg/BATless mice. The result suggests that hepatic ABCA1 may not be a primary contributing factor for perturbations in HDL metabolism in obesity-induced hyperinsulinemia

Unsaturated Fatty Acids Repress the Expression of ATP-Binding Cassette Transporter A1 in HepG2 and FHs 74 Int Cells

Adenosine triphosphate–binding cassette transporter A1 (ABCA1) plays a critical role in the formation and metabolism of high-density lipoproteins (HDLs). Adenosine triphosphate–binding cassette transporter A1 in the liver and small intestine, in particular, accounts for approximately 90% of plasma HDL cholesterol. Therefore, any alterations in the hepatic and intestinal expression of ABCA1 could have a large impact on HDL biogenesis. We tested the hypothesis that ABCA1 expression is regulated differentially by different types of fatty acids in the liver and small intestine. Human hepatoma HepG2 and human small intestine epithelial FHs 74 Int cells were used as an in vitro model. Cells were incubated with saturated and unsaturated fatty acids in the presence or absence of T0901317, a synthetic agonist of liver X receptor. Unsaturated fatty acids decreased ABCA1 protein levels at 100 μmol/L of concentration regardless of the agonist with a minimal effect on messenger RNA abundance. Incubation of HepG2 and FHs 74 Int cells with rottlerin, a protein kinase C δ (PKCδ) inhibitor, increased ABCA1 protein but did not abolish linoleic acid–induced decrease in ABCA1 protein levels. Depletion of PKCδ using small interfering RNA showed decreased ABCA1 protein levels in control, palmitic acid–, and linoleic acid–treated cells, but the repressive effect of linoleic acid was sustained. In conclusion, our results indicate that unsaturated fatty acids regulate ABCA1 expression in HepG2 and FHs 74 Int cells at the posttranscriptional level, and PKCδ is likely to be involved in maintaining ABCA1 protein levels

Entropy of Kaluza-Klein Black Hole from Kerr/CFT Correspondence

We extend the recently proposed Kerr/CFT correspondence to examine the dual conformal field theory of Kaluza-Klein black hole. For the extremal Kaluza-Klein black hole, the central charge and temperature of the dual conformal field are calculated, and the microscopic entropy calculated by using Cardy formula agrees with the Bekenstein-Hawking entropy of extremal Kaluza-Klein black hole. For the non-extremal case, we investigate the hidden conformal symmetry of Kaluza-Klein black hole by studying the near-region wave equation of a neutral massless scalar field, and find the left and right temperatures of dual conformal field theory. Furthermore, the entropy of non-extremal Kaluza-Klein black hole is reproduced by using Cardy formula.Comment: 13pages, no figure, published versio

Lipid Extract of \u3ci\u3eNostoc commune\u3c/i\u3e var. \u3ci\u3esphaeroides\u3c/i\u3e Kützing, a Blue-Green Alga, Inhibits the Activation of Sterol Regulatory Element Binding Proteins in HepG2 Cells

Nostoc commune var. sphaeroides Kützing (N. commune), a blue-green alga, has been used as both a food ingredient and in medicine for centuries. To determine the effect of N. commune on cholesterol metabolism, N. commune lipid extract was incubated at increasing concentrations (25–100 mg/L) with HepG2 cells, a human hepatoma cell line. The addition of N. commune lipid extract markedly reduced mRNA abundance of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and LDL receptor (LDLR) (P \u3c 0.05), with a concomitant decrease in their protein expression (P \u3c 0.001). Reduced HMGR activity by 90% with N. commune lipid extract confirmed the inhibitory role of N. commune in cholesterol synthesis (P \u3c 0.006). To elucidate a molecular mechanism underlying the repression of HMGR and LDLR by N. commune lipid extract, expression of sterol regulatory element binding protein 2 (SREBP-2) was assessed. Whereas mRNA for SREBP-2 remained unchanged, SREBP-2 mature protein was reduced by N. commune (P \u3c 0.009). In addition, N. commune lipid extract also decreased SREBP-1 mature protein by ~30% (P \u3c 0.002) and reduced the expression of SREBP-1-responsive genes such as fatty acid synthase and stearoyl CoA desaturase 1 (SCD-1) (P \u3c 0.05). Therefore, our results demonstrate that N. commune lipid extract inhibits the maturation process of both SREBP-1 and -2, resulting in a decrease in expression of genes involved in cholesterol and fatty acid metabolism

Digitisation of manual composite layup task knowledge using gaming technology

Increased market demand for composite products and shortage of expert laminators is compelling the composite industry to explore ways to acquire layup skills from experts and transfer them to novices and eventually to machines. There is a lack of holistic methods in literature for capturing composite layup skills especially involving complex moulds. This research aims to develop an informatics-based method, enabled by consumer-grade gaming technology and machine learning, to capture and digitise manufacturing task knowledge from skill-intensive hand layup. The digitisation is underpinned by the proposed human-workpiece interaction theory and implemented to automatically extract and decode key knowledge constituents such as layup strategies, ply manipulation techniques, motion mechanics and problem-solving during hand layup, collectively categorised as layup skills. The significance of this research is its potential to facilitate cost-effective transfer of skills from experts to novices, real-time automated supervision of hand layup and automation of layup tasks in the future

Hypocholesterolemic effect of \u3ci\u3eNostoc commune\u3c/i\u3e var. \u3ci\u3esphaeroides\u3c/i\u3e Kützing, an edible blue-green alga

Background Intake of an edible blue-green alga Nostoc commune var. sphaeroides Kützing (N. commune) has been shown to lower plasma total cholesterol concentration, but the mechanisms behind the hypocholesterolemic effect have not been elucidated. Aim of the study To elucidate the mechanisms underlying the cholesterol-lowering effect of N. commune in mice. Methods Male C57BL/6J mice were fed the AIN-93 M diet supplemented with 0 or 5% (wt/wt) dried N. commune for 4 weeks. Lipid levels in the plasma and liver, intestinal cholesterol absorption, and fecal sterol excretion were measured. Expression of hepatic and intestinal genes involved in cholesterol metabolism was evaluated by quantitative realtime PCR. Results N. commune supplementation significantly reduced total plasma cholesterol and triglyceride concentrations by ~20% compared to controls. Intestinal cholesterol absorption was significantly decreased, while fecal neutral sterol output was significantly increased in N. commune–fed mice. mRNA levels of the cholesterol transporters such as Niemann Pick C1 Like 1, scavenger receptor class B type 1, ATP-binding cassette transporters G5 and A1 in small intestine were not significantly different between two groups. Hepatic lipid contents including total cholesterol, triglyceride and free cholesterol in N. commune–fed mice were not significantly altered. However, the expression of cholesterol-modulating genes including sterol regulatory element binding protein-2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase were significantly increased in mice fed N. commune. Conclusions N. commune supplementation exerted a hypocholesterolemic effect in mice, largely in part, by reducing intestinal cholesterol absorption and promoting fecal neutral sterol excretion

Repression of Proinflammatory Gene Expression by Lipid Extract of \u3ci\u3eNostoc commune\u3c/i\u3e var \u3ci\u3esphaeroides\u3c/i\u3e Kützing, a Blue-green Alga, via Inhibition of Nuclear Factor-κB in RAW 264.7 Macrophages

We investigated whether lipid extract from a blue-green alga, N. commune, modulates proinflammatory gene expression in RAW 264.7 macrophages. The cells were incubated with N. commune lipid extract (0–100 μg/mL) and subsequently activated by LPS (100 ng/mL). Quantitative real-time PCR analysis showed that mRNA abundance of proinflammatory mediators, including TNF-α, COX-2, IL-1β, IL-6, and iNOS, was significantly reduced by N. commune lipid extract in a dose-dependent manner. Secretion of TNF-α and IL-1β into cell culture medium was also significantly decreased by N. commune lipid extract. Thin-layer chromatography-densitometry analysis showed that N. commune lipid extract contained approximately 15% of fatty acids. To determine whether the inhibition of proinflammatory mediator production by N. commune lipid extract is primarily conferred by fatty acids in the lipid extract, macrophages were incubated with 100 μg/mL of N. commune lipid extract or 15 μg/mL of a fatty acid mixture, which was formulated to reflect the fatty acid composition of N. commune lipid extract. The fatty acid mixture significantly reduced RNA abundance of TNF-α and COX-2, but to a lesser extent than did the N. commune lipid extract, suggesting the presence of additional bioactive compounds with an anti-inflammatory property in the lipid extract. As NF-κB is a major regulator for the proinflammatory gene expression, we measured its DNA-binding activity. DNA-binding activity of NF-κB was significantly reduced by N. commune lipid extract. In conclusion, our study suggests that N. commune lipid extract represses the expression of proinflammatory genes in RAW 264.7 macrophages, at least in part, by inhibiting the activation of NF-κB pathway

A Census of Baryons and Dark Matter in an Isolated, Milky Way-sized Elliptical Galaxy

We present a study of the dark and luminous matter in the isolated elliptical galaxy NGC720, based on deep X-ray observations made with Chandra and Suzaku. The gas is reliably measured to ~R2500, allowing us to place good constraints on the enclosed mass and baryon fraction (fb) within this radius (M2500=1.6e12+/-0.2e12 Msun, fb(2500)=0.10+/-0.01; systematic errors are <~20%). The data indicate that the hot gas is close to hydrostatic, which is supported by good agreement with a kinematical analysis of the dwarf satellite galaxies. We confirm a dark matter (DM) halo at ~20-sigma. Assuming an NFW DM profile, our physical model for the gas distribution enables us to obtain meaningful constraints at scales larger than R2500, revealing that most of the baryons are in the hot gas. We find that fb within Rvir is consistent with the Cosmological value, confirming theoretical predictions that a ~Milky Way-mass (Mvir=3.1e12+/-0.4e12 Msun) galaxy can sustain a massive, quasi-hydrostatic gas halo. While fb is higher than the cold baryon fraction typically measured in similar-mass spiral galaxies, both the gas fraction (fg) and fb in NGC720 are consistent with an extrapolation of the trends with mass seen in massive galaxy groups and clusters. After correcting for fg, the entropy profile is close to the self-similar prediction of gravitational structure formation simulations, as observed in galaxy clusters. Finally, we find a strong heavy metal abundance gradient in the ISM similar to those observed in massive galaxy groups.Comment: 23 pages, 13 figures, 4 tables. Accepted for publication in the Astrophysical Journal. Minor modifications to match accepted version. Conclusions unchange

The R-process Alliance: First Magellan/MIKE Release from the Southern Search for R-Process-enhanced Stars

Extensive progress has been recently made into our understanding of heavy element production via the $r$-process in the Universe, specifically with the first observed neutron star binary merger (NSBM) event associated with the gravitational wave signal detected by LIGO, GW170817. The chemical abundance patterns of metal-poor $r$-process-enhanced stars provides key evidence into the dominant site(s) of the $r$-process, and whether NSBMs are sufficiently frequent or prolific $r$-process sources to be responsible for the majority of $r$-process material in the Universe. We present atmospheric stellar parameters (using a Non-Local Thermodynamic Equilibrium analysis) and abundances from a detailed analysis of 141 metal-poor stars, carried out as part of the $R$-Process Alliance (RPA) effort. We obtained high-resolution "snapshot" spectroscopy of the stars using the MIKE spectrograph on the 6.5m Magellan Clay telescope at Las Campanas Observatory in Chile. We find 10 new highly enhanced $r$-II (with [Eu/Fe] $> +1.0$), 62 new moderately enhanced $r$-I ($+0.3 <$ [Eu/Fe] $\le +1.0$) and 17 new limited-$r$ ([Eu/Fe] $< +0.3$) stars. Among those, we find 17 new carbon-enhanced metal-poor (CEMP) stars, of which five are CEMP-no. We also identify one new $s$-process-enhanced ([Ba/Eu ]$> +0.5$), and five new $r/s$ ($0.0 <$ [Ba/Eu] $< +0.5$) stars. In the process, we discover a new ultra metal-poor (UMP) star at [Fe/H]=$-$4.02. One of the $r$-II stars shows a deficit in $\alpha$ and Fe-peak elements, typical of dwarf galaxy stars. Our search for $r$-process-enhanced stars by RPA efforts, has already roughly doubled the known $r$-process sample.Comment: 17 pages, 9 figures, 6 tables, Accepted for publication in Ap